BOONE—In science, the pursuit to prove one hypothesis often leads to a different discovery.

Such was the case for researchers from Appalachian State University, Dole Food Company and N.C. State University’s Plants for Human Health Institute.

A runner drinks a blueberry and green tea polyphenol-soy protein complex prior to participating in a study conducted by Appalachian State University researchers and others at the NC Research Campus in Kannapolis. (Photo submitted)Researchers found that extreme exercise enhanced the body’s “leaky gut” effect, allowing more of the beneficial polyphenols to enter the body. In addition, an “after burn” effect meant the runners’ metabolism continued to burn additional calories as long as 14 hours after running. (Photo submitted)

The researchers were testing the efficacy of a protein drink infused with beneficial polyphenols from blueberries and green tea as an alternative to taking NSAIDS (nonsteroidal anti-inflammatory drugs) to reduce inflammation and oxidative stress associated with extreme exercise.

During a two-week study, long-distance runners were given either the infused soy protein complex or just the protein complex. The runners ingested the soy protein complex twice a day, including the three days that they ran for two-and-a-half hours. Each dose was the equivalent of consuming three cups of blueberries and just over a cup of brewed green tea.

What resulted was the first evidence in a human clinical trial of enhanced polyphenolic absorption through the colon following exercise, rather than the small intestine. In addition, runners in the treatment group experienced increased fat oxidation 14 hours after exercise.

The study’s authors published their results, titled Influence of a Polyphenol-Enriched Protein Powder on Exercise-Induced Inflammation and Oxidative Stress in Athletes: A Randomized Trial Using a Metabolomics Approach, in PlosOne, an inclusive, peer-reviewed, open-access resource from the Public Library of Science. The authors were David C. Nieman, Dr.P.H., FACSM, director of the Appalachian State University Human Performance Laboratory in the College of Health Science; Mary Ann Lila, Ph.D., director of the North Carolina State University Plants for Human Health Institute; and Nicholas Gillitt, Ph.D., director of nutrition research for Dole Food Company.

They found that during extreme exercise the polyphenol compounds enter the body from the colon, further reinforcing the benefit of exercise combined with eating fruits and vegetables containing polyphenols.

“If you are willing to exercise hard enough to sweat, gut permeability increases, and you get more of these beneficial compounds coming back into your body,” Nieman said.

“Everybody thinks polyphenols get through by being absorbed in the small intestine, classic bioavailability if you like, but research shows hardly any polyphenols get through that way,” commented Gillitt. “What we have observed is that they actually make it further down into the colon and get into the system that way. It is an alternative explanation to why these compounds might be in concentrations that could be beneficial to the body.”

Polyphenols are a class of bioactive compounds in fruits and vegetables that are linked to health benefits, such as lowering blood pressure and blood glucose, reducing inflammation and fighting off the damaging effects of free radicals. They were thought to enter the blood stream primarily through the small intestine, but recent studies including this one are placing more importance on the colon.

The finding is relevant, Nieman said, because combining polyphenol intake with exercise not only increases gut permeability and allows more polyphenols into the body, the specific polyphenols that were found in the athletes’ blood stream are known to have anti-oxidant and anti-inflammatory effects.

“Following intense and prolonged running, athletes experience transient inflammation, oxidative stress and immune dysfunction,” Nieman said. “Metabolomics, a new technology that simultaneously measures changes in hundreds of metabolites, showed that the majority of the polyphenols went to the colon where the bacteria broke them down into smaller pieces. The intense exercise increased gut permeability, promoting their transfer into the body in much higher amounts than before the exercise.”

The research team reported in their findings that future research is warranted to determine if longer-term polyphenol enrichment of the athletic diet mitigates the physiologic stress of heavy exertion, improves the speed of recovery, produces other benefits such as lowered incidence of acute respiratory illnesses and has comparable effects in a variety of athletic groups.

“It is useful to show in human clinical trials that when you eat fruits and vegetables, these compounds can flood into the system, even if it is not by the classic way everyone thought they did,” Gillitt said.

“We have already shown the carbohydrates in bananas provide a good source of energy during exercise. This study shows the polyphenols found in fruits and vegetables could also be helpful to athletes who experience high levels of oxidative stress and inflammation,” he said.

The study was part of Nieman’s and others at the N.C. Research Campus work to find the ideal combination of fruits and vegetables to boost the immune system of extreme athletes.

“We are very interested in moving forward with research looking for an alternative to taking nonsteroidal anti-inflammatory drugs,” Nieman said. “NSAIDS are the most common drug that both athletes and warfighters use, often in very large quantities.”

Research conducted by Nieman and others at Appalachian showed that chronic ibuprofen users had severe negative effects following the Western States 100 mile race, including mild kidney dysfunction and more inflammation. The combination of taking high doses of NSAIDs with exercise also damaged the lining of the colon, allowing bacteria to enter the blood stream and cause mild endotoxicity, which raised inflammation by 30-40 percent. There also was more oxidative stress and free radical damage to the lipid part of the cell membrane.

Another study found that a combination of Quercetin, green tea and fish oil did act as an ibuprofen substitute in reducing exercise-related inflammation. Quercetin contains beneficial plant and vegetable compounds that help boost the immune system.

“That led us to believe if we started looking more at fruit or green tea extracts we could develop a ‘cocktail’ of beneficial polyphenols and flavonoids,” Nieman said.

The N.C. Research Campus scientists are planning additional collaborative studies to build on their findings in order to better understand the physiological mechanisms at play and the potential applications for athletes and consumers.

About the NC Research Campus

The NC Research Campus (NCRC) is home to corporate, academic and healthcare partners focused on advancing science at the intersection of human health, agriculture and nutrition. The NCRC is located on a 350-acre campus in Kannapolis, just north of Charlotte, and has more than a million square feet of lab and office space under management that includes five buildings.

The Appalachian State University Human Performance Laboratory at the NCRC is a national leader in the area of nutrition and exercise immunology. Researchers work with trained and amateur athletes, corporate collaborators and sponsors as well as community participants to investigate the influence of plant molecules on age-related loss of muscle mass (sarcopenia), muscle mitochondrial biogenesis and exercise-induced changes in immune function, oxidative stress and inflammation. The lab is part of the university’s College of Health Sciences.

The North Carolina State University Plants for Human Health Institute integrates research in metabolomics, biochemistry, pharmacogenomics, plant breeding and post-harvest physiology to improve the health-enhancing properties of food crops to decrease the incidence of chronic disease and to increase farm sustainability and profitability.

The Dole Nutrition Research Laboratory identifies and quantifies phytochemicals in the company’s fruits and vegetable portfolio in order to help prevent the development of many common diseases such as heart disease, cancer and diabetes. The Dole laboratory also investigates how to enhance the nutritional benefits of its products by supporting the research requests of the company’s divisions and collaborating with NCRC partners.